Question

How are some bacteria resistant to penicillins?

Answer 1

Penicillins are a class of beta lactam antibiotics which inhibit the cell wall biosynthesis of bacteria. Peptidoglycan is an important cell wall component providing structural integrity to the bacteria. Penicillins inhibit the peptidoglycan biosynthesis by blocking the enzyme D,D transpeptidase responsible for the peptidoglycan cross-linking. D,D- transpeptidase are also known as penicillin binding proteins. Penicillins irreversibly binds with the D,D-transpeptidase enzyme leading to the inhibition of PG biosynthesis.As a result, the cell wall of the bacterial will lyse due to increased osmotic pressure from the cytoplasm. Many of the bacteria are now resistant to penicillin mainly due to the following reasons.

1) Production of beta lactamase enzymes: Beta lactamases are enzymes which are produced by the bacteria. These enzymes are capable of degrading beta lactam antibiotics including penicillins by hydrolyzing the beta lactam ring of the antibiotic and makes it ineffective.

2) Production of altered D,D-transpeptidase enzymes: Some bacteria are capable of producing evolved D,D-transpeptidase enzymes. Thus, penicillins will not be able to bind effectively with the enzyme.

3) Restriction of drug transport and efflux pumps: Some of the bacteria decrease the permeability of the cell wall for penicillin leading to restricted transport of the drug into the bacterial cell. Some other bacteria have efflux pumps which pumps the drug out of the bacterial cells and therefore the antibiotic cannot bind with the target molecule.

4) Production of L,D-transpeptidases: Many of the bacteria are now have a second type of peptidoglycan cross-linking mediated by L,D transpeptidase enzymes. Therefore, even if penicillin inhibit the D,D transpeptidase enzymes and their cross-linkages, the bacteria will survive with this novel peptidoglycan cross-linkages.

All these above mentioned mechanisms by the bacteria confers resistance to penicillin antibiotics.